Prognostic Significance of Tumor-Infiltrating Lymphocytes and High-Risk Human Papillomavirus in Ocular Sebaceous Carcinoma: A Comprehensive Analysis.

High-risk human papillomavirus (hrHPV) and tumor-infiltrating lymphocytes (TILs) are known to have prognostic significance in oropharyngeal squamous cell carcinoma. However, their significance in ocular sebaceous carcinoma (OSC) remains unverified because of the rarity of the condition. This study aimed to investigate the association between clinicopathologic features, biomarkers, and hrHPV infection and their potential to predict prognosis in OSC patients. We analyzed the clinicopathologic features of 81 OSC patients from Asan Medical Center between 2000 and 2022. Seventeen biomarkers and hrHPV were examined using immunohistochemistry and DNA in situ hybridization on tissue microarray cores. hrHPV was identified in 31 cases (38.3%). Univariate analysis revealed that hrHPV infection was associated with comedonecrosis (P = .032), high Ki-67 labeling index (≥30%, P = .042), lower expression of E-cadherin (P = .033), and loss of expression of zinc finger protein 750 (P = .023). Multivariate analysis revealed that loss of expression of zinc finger protein 750 (P = .026) remained an independently associated factor for hrHPV. Progression-free survival analysis was performed on 28 patients who were continuously observed for more than 5 years. During a median follow-up duration of 86 months, recurrence or metastasis developed in 14 patients (50%) within the survival cohort, occurring at a median time of 48 months after excision. Univariate analysis indicated that recurrence or metastasis was associated with tumor size (P = .010), high TILs (≥10%; P = .025), lymphovascular invasion (P = 0.043), site of origin (P = .025), and high expression of bcl-2-associated athanogene 3 (P = .039). Multivariate analysis demonstrated that high TILs (P = .017) and site of origin (P = .025) were independent prognostic factors. The prognosis of OSC was hrHPV-independent, and a better prognosis was associated with the site of origin in the order of the gland of Zeis, meibomian gland, and multicentric site, as well as with high TILs.

Favorable clinical efficacy of cytotoxic chemotherapy in patients with progressive desmoid tumors: a retrospective real-world study.

BACKGROUND: The real-world evidence about the efficacy of cytotoxic chemotherapy in desmoid tumors is still limited. We investigated the efficacy of chemotherapy in the treatment of recurrent or progressive desmoid tumors. METHODS: The patients with desmoid tumors who had received cytotoxic chemotherapy between November 2007 and June 2020 in two tertiary hospitals in Korea were reviewed. RESULTS: A total of 25 patients were included in the analysis. The most common primary tumor site was the intra-abdominal or pelvic cavity (56%), followed by the trunk and abdominal wall (24%), extremities (16%), and head and neck (4%). Sixty percent of the patients had familial adenomatous polyposis and 76% received doxorubicin plus dacarbazine. The objective response rate and disease control rate was 64% (95% confidence interval [CI]: 40.7-82.8) and 96% (95% CI: 77.2-99.9), respectively. With the median follow-up time of 55 months (95% CI: 41.0-68.2), the 3-year PFS rate was 65% (95% CI: 41.1-80.5), and the 3-year OS rate was 89% (95% CI: 63.8-97.3). Grade 3 or 4 hematologic adverse events were reported in 14 patients, all of which were manageable. CONCLUSION: Our real-world evidence suggests that doxorubicin-based cytotoxic chemotherapy can be an effective treatment option for recurrent and progressive desmoid tumors with respect to favorable clinical outcomes.

The relationship between organising pneumonia and invasive mould disease in patients with haematologic malignancy.

BACKGROUND: Organising pneumonia (OP) is reported in patients with haematologic malignancy suspected of having invasive mould disease, yet little is known about this relationship. OBJECTIVE: To investigate molecular evidence of invasive mould pneumonia in paraffin-embedded lung tissues from histologically diagnosed OP patients with suspected invasive mould pneumonia. PATIENTS/METHODS: Patients with haematologic malignancy suspected to have invasive pulmonary mould disease who underwent lung biopsy at a tertiary hospital, Seoul, South Korea, between 2008 and 2020, were retrospectively reviewed. To find molecular evidence of fungal infection, PCR assay was used to detect Aspergillus- and Mucorales-specific DNA within OP lung tissue sections. RESULTS: Forty-seven patients with suspected invasive mould pneumonia underwent lung biopsy and 15 (32%) were histologically diagnosed as OP without any evidence of fungal hyphae. Of these 15 patients, 3 (20%) received allogenic haematopoietic stem cell transplantation prior to developing OP. Before biopsy, 2 and 13 patients had probably and possible invasive mould disease, respectively. The median antifungal treatment length was 81 [8-114] days, and the median steroid treatment dosage was 0.35 mg/kg/day for 36 days (methylprednisolone equivalent doses), respectively. After biopsy, three patients with possible invasive mould infection revealed probable invasive pulmonary aspergillosis. From the 15 paraffin-embedded lung tissues, 6 (40%) exhibited positive PCR assay results for detecting Aspergillus- and Mucorales-specific DNA. CONCLUSIONS: More than one third of OP cases in patients with suspected invasive mould pneumonia exhibited molecular evidence of invasive mould infection by fungus-specific PCR in lung tissues, likely associated with concurrent or prior fungal infection.

Comparison of isolated respiratory and extrarespiratory mucormycosis: a 21-year observational study of 44 cases.

OBJECTIVES: This study aimed to compare the clinical characteristics and outcomes of patients with isolated respiratory and extrarespiratory mucormycosis. METHODS: Adult patients diagnosed with proven or probable invasive mucormycosis in a tertiary hospital in South Korea, between 1999 and 2020 were retrospectively reviewed. We compared the clinical, mycological characteristics, and outcomes of patients with isolated respiratory mucormycosis (IRM) and those with extrarespiratory mucormycosis (ERM). RESULTS: A total of 44 patients including 32 (72%) with IRM, and 12 (27%) with ERM were enrolled. Of these, 38 (86%) were classified as proven and 6 (14%) as probable invasive mucormycosis according to the EORTC/MSG criteria. Univariate analysis exhibited that old age, surgery, and intensive care unit were associated with ERM, and multivariable analysis revealed that variable associated with ERM was intensive care unit (aOR 9.80; 95% CI 2.07-46.35; P = 0.004). There were no significant differences in 90-day mortality between patients with IRM and ERM (38% vs 50%, P = 0.45). In multivariable analysis, neutropenia (aOR 6.88; 95% CI 1.67-28.27; P = 0.01) was an independent risk factor for 90-day mortality. CONCLUSIONS: More than a quarter of patients with mucormycosis had extrarespiratory manifestations, especially in patients who were admitted to intensive care unit. The mortality of the patients with ERM was comparable to that of the patients with IRM, although the patients with ERM received ICU care more frequently.

Serial changes of CT findings in patients with chronic hypersensitivity pneumonitis: imaging trajectories and predictors of fibrotic progression and acute exacerbation.

OBJECTIVES: To evaluate the longitudinal changes of chest CT findings in patients with chronic hypersensitivity pneumonitis (HP) and identify risk factors for fibrotic progression and acute exacerbation (AE). METHODS: This retrospective study included patients with chronic HP with follow-up CT. Baseline and serial follow-up CT were evaluated semi-quantitatively. Fibrosis score was defined as the sum of the area with reticulation and honeycombing. The modified CT pattern of Fleischner Society idiopathic pulmonary fibrosis diagnostic guidelines was evaluated. Cox proportional hazards regression was performed to determine significant variables associated with fibrotic progression and AEs. RESULTS: Of 91 patients, mean age was 59.1 years and 61.5% were women. The median follow-up period was 4.9 years. Seventy-nine patients (86.8%) showed fibrotic progression with persistent areas of mosaic attenuation, finally replaced by fibrosis, and 20 (22.0%) developed AE. Baseline fibrosis score and CT pattern of usual interstitial pneumonia (UIP)/probable UIP were independent risk factors for predicting fibrotic progression (hazard ratio [HR] = 1.05, 95% confidence interval [CI] = 1.02-1.09, p < 0.001, for fibrosis score; HR = 2.50, CI = 1.50-4.16, p < 0.001, for CT pattern) and AEs (HR = 1.07, CI = 1.01-1.13, p = 0.019, for fibrosis score; HR = 5.47, CI = 1.23-24.45, p = 0.026, for CT pattern) after adjusting clinical covariables. CONCLUSION: Fibrotic progression and AE were identified in 86.8% and 22.0% of patients with chronic HP. Fibrosis score and CT pattern of UIP/probable UIP on baseline chest CT may predict fibrotic progression and AE. KEY POINTS: • Most patients (87%) showed fibrotic progression on long-term follow-up with persistent areas of mosaic attenuation that were finally replaced by fibrosis at a later stage. • One-fifth of patients (22%) experienced acute exacerbation associated with worse prognosis. • Fibrosis score (sum of reticulation and honeycombing) and CT pattern of UIP/probable UIP on baseline CT were independent predictors for predicting fibrotic progression and acute exacerbation.

Pleuropulmonary Blastoma with Hotspot Mutations in RNase IIIb Domain of DICER 1: Clinicopathologic Study of 10 Cases in a Single-Institute Experience.

INTRODUCTION: Pleuropulmonary blastoma (PPB) is a rare sarcomatous malignancy involving the lung and pleura which occurs in early childhood. Cystic PPB in the early stage can be misdiagnosed as other cystic diseases. Early detection of this entity is important for appropriate treatment and prevention of disease progression. Hotspot mutations in the ribonuclease IIIb (RNase IIIb) domain of DICER1 have been reported to have a crucial role as genetic factors of PPB and DICER1 familial syndrome. We reviewed the clinicopathologic findings of PPB and the status of DICER1 hotspot mutation and patients' clinical course. METHODS: We retrospectively reviewed all patients with histologically confirmed PPB at Asan Medical Center between 2000 and 2017. Ten cases were identified in the database, and their clinicopathologic parameters were evaluated. PPB was classified into the following 3 pathologic subtypes: type I (purely cystic), type II (mixed cystic and solid), and type III (entirely solid). The status of DICER1 mutation in 2 hotspot regions of the RNase IIIb domain was evaluated by Sanger sequencing. RESULTS: The most frequent PPB type was II (6 cases), followed by I and III (2 cases each). The age at diagnosis ranged from 16 months to 15 years. All patients underwent surgery, and all patients received adjuvant or neoadjuvant chemotherapy. Four of 7 patients had missense mutations in the RNase IIIb hotspot; the base and predicted corresponding amino acid changes were c.5113 G>A (p.E1705K), c.5407 G>A (p.E1803K), c.5425 G>A (p.G1809R), and c.5428 G>T (p.D1810Y). There was no particular association between the presence of the hotspot mutation and histologic type. Nine patients survived with no evidence of disease for a median interval of 93 (range, 13-199) months. Only 1 patient diagnosed with type III PPB at the age of 18 years had recurrence after 20.8 months and eventually died 66 months after the initial diagnosis. CONCLUSIONS: Late detection of solid PPB is associated with poor prognosis. Considering the rarity of PPB disease and the importance of DICER1 hotspot mutation in pathogenesis, DICER1 hotspot mutation testing and identification in the early cystic stage can improve patient outcomes.

Prognostic Implication of Diagnostic Confidence Level in Patients with Fibrotic Hypersensitivity Pneumonitis.

BACKGROUND: Hypersensitivity pneumonitis (HP) has various clinical courses and outcomes, but the prognostic factors are not well-defined. Vasakova et al. [Am J Respir Crit Care Med. 2017 Sep;196(6):680-9] have proposed a diagnostic algorithm that categorized suspected patients according to the level of confidence in the diagnosis. This study aimed to investigate whether the confidence level of clinical diagnosis has prognostic implication in patients with fibrotic HP. METHODS: This study included 101 biopsy-proven fibrotic HP patients diagnosed between 2002 and 2017. The patients were retrospectively classified into confident, probable, possible, and unlikely chronic HP, according to the confidence level in the diagnostic criteria/algorithm. The survival and forced vital capacity (FVC) changes were compared between the groups. Risk factors for mortality were analysed using a Cox proportional hazard model. RESULTS: The median follow-up duration was 67.6 months. The mean age was 60.4 years, and percentages of women were 60.4%. When classified based on the diagnostic criteria/algorithm, possible HP was the most common (51.5%), followed by probable (26.7%), confident (9.9%), and unlikely HP (6.9%). Distinctive survival curves were found according to the diagnostic confidence level, showing the worst outcome in unlikely chronic HP (median survival, 30.2 months). In a multivariable Cox analysis, unlikely HP was a significant predictor of poor survival (hazard ratio, 4.652; 95% confidence interval, 1.231-17.586; p = 0.023), after adjustment for age, body mass index, FVC, and diffusing capacity. CONCLUSIONS: The diagnostic confidence level may predict clinical outcomes in patients with HP. Unlikely HP was shown to have a significantly poorer survival than other diagnostic confidence levels.

Long-term clinical course and outcomes of immunoglobulin G4-related lung disease.

BACKGROUND: Immunoglobulin G4-related lung disease (IgG4-RLD) is the pulmonary manifestation of a systemic fibroinflammatory disease characterized by lymphoplasmacytic infiltration with an abundance of IgG4-positive plasma cells. Long-term clinical course and outcomes of IgG4-RLD remain unclear. We aimed to identify clinical characteristics, treatment outcomes, and longitudinal pulmonary function changes in patients with IgG4-RLD according to the radiologic classification. METHODS: Chest computed tomography findings of 37 subjects were classified into five subtypes: solid nodular, bronchovascular, alveolar interstitial, round ground glass opacity, and alveolar consolidative. Radiologic treatment outcomes and longitudinal pulmonary function changes were compared among the different radiologic subtypes. RESULTS: The mean age of the subjects was 55.6 years, and 78.4% were male. Among the five radiologic subtypes, alveolar consolidative and solid nodular type were most common, accounting for approximately 29.7% each of the total cases. Prednisone with or without azathioprine was administered to 31 patients (median treatment duration 14 months). In the treated patients, serial images showed complete response or partial response in 77.4%. However, relapse was documented in 25.0% of those who showed complete or partial response. In patients whose longitudinal lung function data were available (n = 20), the lung function was found to be stable during follow-up. Alveolar consolidative type showed the highest complete response rate, whereas alveolar interstitial type showed the lowest response rate, either complete or partial. CONCLUSIONS: Most patients showed a favorable outcome with regards to radiologic improvement and maintenance of pulmonary function; however, the response differed according to the radiologic subtype.

Pleuroparenchymal fibroelastosis in patients with idiopathic pulmonary fibrosis.

BACKGROUND AND OBJECTIVE: PPFE is characterized by fibrosis in the pleura and subpleural lung parenchyma in the upper lobes, while other types of ILD, mainly UIP, can be observed in about half of the patients in their lower lobes. The aim of this study was to evaluate the clinical significance of the radiologically defined PPFE in patients with IPF. METHODS: Clinical data and chest CT images were retrospectively analysed in 445 patients with IPF (biopsy-proven cases, n = 165). The radiological criteria of PPFE were defined as follows: (i) bilateral subpleural dense fibrosis with or without pleural thickening in the upper lobes, (ii) evidence of disease progression and (iii) no clinical evidence of identifiable aetiologies. RESULTS: The median follow-up period was 43.0 months. The mean age of the patients was 66.4 years and 76.4% were male. PPFE was identified in 28 patients (6.3%). The PPFE group showed lower BMI and lung function (FVC and TLC) at baseline, more frequent pneumothorax and pneumomediastinum, higher decline rates in lung function and poorer prognosis during follow-up than the no-PPFE group. PPFE was an independent risk factor (HR = 2.953, 95% CI: 1.350-6.460, P = 0.007) for pneumothorax or pneumomediastinum, but not for mortality in patients with IPF. CONCLUSION: Among patients with IPF, the PPFE group, when compared to the no-PPFE group, showed lower BMI and lung function and showed more frequent complications and poorer survival during follow-up.

Long-term clinical course and outcome of interstitial pneumonia with autoimmune features.

BACKGROUND AND OBJECTIVE: Idiopathic interstitial pneumonia (IIP) with autoimmune features that does not fulfil connective tissue disease (CTD) criteria has been recently defined as interstitial pneumonia with autoimmune features (IPAF). However, its long-term clinical course and outcome are poorly understood. METHODS: We included consecutive patients diagnosed with IIP (n = 586) or CTD-related interstitial lung disease (CTD-ILD, n = 149). Some patients with IIP were reclassified as IPAF based on recent guidelines. RESULTS: The median follow-up period was 45 months. Among the IIP patients, 109 (18.6%) were reclassified as IPAF. Compared to the non-IPAF-IIP group, the IPAF group had slower diffusing capacity of the lung for carbon monoxide (DLCO ) and total lung capacity declines, and more frequent CTD development during follow-up periods. The prognosis of the IPAF was better than that of the non-IPAF-IIP and similar to that of the CTD-ILD. IPAF was associated with better prognosis in the IIP cohort on univariate but not on multivariate analysis. Usual interstitial pneumonia (UIP) pattern, old age and low DLCO independently predicted mortality in the IPAF group. CONCLUSION: Compared to the non-IPAF-IIP group, the IPAF group had slower lung function declines and more frequent CTD development during follow-up. Although the prognosis of IPAF group was better than that of non-IPAF-IIP group and similar to that of CTD-ILD group, it showed poor prognosis in patients with old age, UIP pattern, and low DLCO .

Risk factors for mortality in patients with pulmonary mucormycosis.

BACKGROUND: Pulmonary mucormycosis (PM) represents a serious burden in terms of morbidity and mortality in immunocompromised patients. Studies of prognostic factors in patients with PM are limited and have involved small numbers of patients. METHODS: Adult patients diagnosed with proven and probable PM according to the modified definitions of the EORTC/MSG 2008 in a tertiary hospital in Seoul, South Korea, between 2008 and 2019 were retrospectively enrolled. RESULTS: A total of 49 patients including 31 (63%) with proven PM and 18 (37%) with probable PM were enrolled. The 90-day mortality rate was 49% (24/49). Neutropenia, thrombocytopenia, use of voriconazole at clinical suspicion, positivity of non-sterile culture, use of steroid and treatment without surgery were more common in fatal cases than non-fatal cases. Voriconazole use at clinical suspicion for invasive mould pneumonia (OR 6.91, P = .01) and prolonged neutropenia (OR 4.86, P = .03) were independent risk factors for mortality. Voriconazole use at clinical suspicion was associated with positive galactomannan (GM) assay (OR 5.93, P = .02) and history of invasive pulmonary aspergillosis (OR, 6.88, P = .05). CONCLUSION: About half of the patients with PM died within 90 days of diagnosis, and fatal outcomes were common in patients with prolonged neutropenia and empirical voriconazole use. Caution is needed in using voriconazole even in patients with positive GM results and prior histories of invasive pulmonary aspergillosis in whom PM cannot be ruled out by differential diagnosis.

Bone oxaloma-a localized manifestation of bone oxalosis.

Oxalosis is a metabolic disorder characterized by the accumulation of calcium oxalate deposits in various organ systems. Bone oxalosis is a systemic manifestation of oxalosis, in which calcium oxalate deposits accumulate in the skeletal system. This report describes a 69-year-old female patient who presented with right hip pain and was later found to have an osseous mass-like lesion in the right proximal femur, with radiographic findings resembling those of a benign bone tumor. CT-guided biopsy and surgical biopsy showed that the mass had pathologic findings typical of bone oxalosis. Because the patient had no predisposing factors for systemic oxalosis and had no hyperoxalemia or hyperoxaluria, she could be diagnosed with localized bone oxalate deposition disease or bone oxaloma rather than bone oxalosis. This is the first report of this clinical entity to present as a benign-appearing bone mass and without any predisposing systemic causes.

Added value of diffusion-weighted imaging to conventional MRI for predicting fascial involvement of soft tissue sarcomas.

OBJECTIVES: This study was conducted to evaluate the added value of diffusion-weighted imaging (DWI) to conventional magnetic resonance imaging (MRI) for predicting fascial involvement of soft tissue sarcomas located in close proximity to fascial boundaries. METHODS: This retrospective study included 29 patients with surgically resected soft tissue sarcomas located in proximity to deep fascia and with a curvilinear tail-like hyperintensity in the adjacent fascia on T2-weighted images. All patients underwent conventional MRI and DWI at 3.0 T and had detailed histologic reports on involvement of fascia. Two musculoskeletal radiologists with 21 and 1 year of experience independently reviewed conventional MRI and conventional imaging with added DWI. Readers scored their confidence for tumor involvement of fascia using a three-point scale. Diagnostic performance (area under the curve [Az]) of the two MRI sets was assessed with receiver-operating characteristic curve analysis. RESULT: Fascial involvement was present in 22/29 patients (75.9%). Both readers showed improvement in diagnostic performance with the addition of DWI (Az, from 0.545 to 0.792 and from 0.646 to 0.792 for reader 1 and reader 2, respectively). Adding DWI did not improve sensitivity or specificity for either reader (p > 0.05). Interobserver agreement for the confidence scores improved from fair to moderate with the addition of DWI (κ, from 0.390 to 0.560). CONCLUSIONS: Adding DWI to conventional MRI improved diagnostic performance on prediction of fascial involvement of soft tissue sarcomas located in proximity to fascia, without significant improvement in sensitivity or specificity. KEY POINTS: • Adding DWI to conventional MRI improved readers' confidence level for the prediction of fascial involvement of soft tissue sarcomas that are close to the deep fascia. • Addition of DWI also improved interobserver agreement. • Conversely, compared with conventional MRI, adding DWI did not significantly improve the sensitivity or specificity for the detection of fascial involvement.

Genomic profiles of lung cancer associated with idiopathic pulmonary fibrosis.

Little is known about the pathogenesis or molecular profiles of idiopathic pulmonary fibrosis-associated lung cancer (IPF-LC). This study was performed to investigate the genomic profiles of IPF-LC and to explore the possibility of defining potential therapeutic targets in IPF-LC. We assessed genomic profiles of IPF-LC by using targeted exome sequencing (OncoPanel version 2) in 35 matched tumour/normal pairs surgically resected between 2004 and 2014. Germline and somatic variant calling was performed with GATK HaplotypeCaller and MuTect with GATK SomaticIndelocator, respectively. Copy number analysis was conducted with CNVkit, with focal events determined by Genomic Identification of Significant Targets in Cancer 2.0, and pathway analysis (KEGG) with DAVID. Germline mutations in TERT (rs2736100, n = 33) and CDKN1A (rs2395655, n = 27) associated with idiopathic pulmonary fibrosis risk were detected in most samples. A total of 410 somatic mutations were identified, with an average of 11.7 per tumour, including 69 synonymous, 177 missense, 17 nonsense, 1 nonstop and 11 splice-site mutations, and 135 small coding indels. Spectra of the somatic mutations revealed predominant C > T transitions despite an extensive smoking history in most patients, suggesting a potential association between APOBEC-related mutagenesis and the development of IPF-LC. TP53 (22/35, 62.9%) and BRAF (6/35, 17.1%) were found to be significantly mutated in IPF-LC. Recurrent focal amplifications in three chromosomal loci (3q26.33, 7q31.2, and 12q14.3) and 9p21.3 deletion were identified, and genes associated with the JAK-STAT signalling pathway were significantly amplified in IPF-LC (P = 0.012). This study demonstrates that IPF-LC is genetically characterized by the presence of somatic mutations reflecting a variety of environmental exposures on the background of specific germline mutations, and is associated with potentially targetable alterations such as BRAF mutations. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Diagnostic performance of immunohistochemistry for the aspergillosis and mucormycosis.

OBJECTIVE: To investigate the accuracy of immunohistochemistry (IHC) tests for distinguishing between mucormycosis and aspergillosis and compare the clinical characteristics of mucormycosis patients according to galactomannan (GM) results. METHODS: We evaluated diagnostic performance of IHC test with tissue sections of patients with culture-proven invasive fungal infection. In addition, we conducted PCR assay with tissue sections of mucormycosis patients with positive GM results to evaluate the possibility of co-infection. RESULTS: In culture-proven mucormycosis (n = 13) and aspergillosis (n = 20), the sensitivity and specificity of IHC test were both 100% for mucormycosis and 85% and 100%, respectively, for aspergillosis. Among the 53 patients who met the modified criteria for proven mucormycosis and had GM assay results, 24 (45%) were positive. Compared with those with negative GM results (n = 29), mucormycosis patients with positive GM results had significantly higher incidence of gastrointestinal tract infections (6/24 [25%] vs 0/29 [0%], P = .006) and were more likely to be histomorphologically diagnosed as aspergillosis (7/24 [29%] vs 2/29 [7%], P = .06). PCR assay amplified both Aspergillus- and Mucorales-specific DNA in 6 of these 24 cases. CONCLUSIONS: Immunohistochemistry tests seem useful for compensating for the limitations of histomorphologic diagnosis in distinguishing between mucormycosis and aspergillosis. Some proven mucormycosis patients with positive GM results had histopathology consistent with aspergillosis and gastrointestinal mucormycosis. In addition, about one quarter of these patients revealed the evidence of co-infection with aspergillosis by PCR assay.

Dual loss of USP10 and p14ARF protein expression is associated with poor prognosis in patients with small intestinal adenocarcinoma.

Oncogene-induced senescence occurs following oncogene activation in normal cells and is considered as a critical tumor-suppressing mechanism. Ubiquitin-specific protease 10 (USP10) has been reported to play a vital role in oncogene-induced senescence via the deubiquitination-dependent stabilization of p14ARF. However, knowledge of the clinical significance of USP10 and p14ARF expression in patients with small intestinal adenocarcinoma is limited. To study the clinical significance of USP10 and p14ARF expression, we performed immunohistochemistry for USP10 and p14ARF on 195 surgically resected small intestinal adenocarcinoma specimens. Furthermore, we performed methylation analysis on five small intestinal adenocarcinoma samples and matched adjacent normal intestinal tissue samples. UPS10 ( p = 0.023) and p14ARF ( p = 0.007) expression were significantly decreased in adenocarcinoma in comparison with normal tissue. The loss of USP10 was observed in 124/194 (63.9%) of small intestinal adenocarcinoma samples and was correlated with a higher pT stage ( p = 0.044), lymphatic invasion ( p = 0.033), and the absence of sporadic adenoma ( p = 0.024) and peritumoral dysplasia ( p = 0.019). p14ARF expression was downregulated in 75/195 (38.5%) of small intestinal adenocarcinoma samples and was associated with vascular ( p = 0.011) and lymphatic ( p = 0.013) invasions. The loss of USP10 expression was associated with the loss of p14ARF expression ( r = 0.342, p < 0.001). Multivariate survival analysis revealed that the combined loss of USP10 and p14ARF expression could be an independent prognostic factor for overall survival in small intestinal adenocarcinoma. Furthermore, the aberrant hypermethylation of the USP10 and p14ARF promoter could be a key mechanism for the downregulation of USP10 and p14ARF proteins in small intestinal adenocarcinoma. These findings suggest that the dual loss of USP10 and p14ARF could be used as a prognostic indicator of small intestinal adenocarcinoma.

Humidifier disinfectant-associated lung injury in adults: Prognostic factors in predicting short-term outcome.

OBJECTIVES: To identify clinical and radiologic findings that affect disease severity and short-term prognosis of humidifier disinfectant-associated lung injury in adults and to compare computed tomography (CT) findings between the patients with and without death or lung transplantation. METHODS: Fifty-nine adults (mean age, 34 years; M/F = 12:47) were enrolled in this retrospective study. Medical records and prospective surveillance data were used to assess clinical and radiological factors associated with a poor clinical outcome. Multivariate generalized estimating equation models were used to analyse serial CT findings. Overall cumulative major events including lung transplantation and mortality were assessed using the Kaplan-Meier method. RESULTS: Almost half needed ICU admission (47.5 %) and 17 died (28.8 %). Young age, peripartum and low O2 saturation were factors associated with ICU admission. On initial chest radiographs, consolidation (P < 0.001) and ground-glass opacity (P = 0.01) were significantly noted in patients who required ICU admission. CT findings including consolidation (odds ratio (OR), 1.02), pneumomediastinum (OR, 1.66) and pulmonary interstitial emphysema (OR, 1.61) were the risk factors for lung transplantation and mortality. CONCLUSION: Clinical and radiologic findings are related to the risks of lung transplantation and mortality of humidifier disinfectant-associated lung injury. Consolidation, pneumomediastinum and pulmonary interstitial emphysema were short-term prognostic CT findings. KEY POINTS: • Young age, peripartum and low O 2 saturation were associated with ICU admission. • Consolidation, pneumomediastinum and pulmonary interstitial emphysema were short-term prognostic CT findings. • Consolidation and ground-glass opacity disappeared within 3 months and replaced by centrilobular nodules. • Radiologic findings are related to the outcome of humidifier disinfectant-associated lung injury.

Association between the CpG island methylator phenotype and its prognostic significance in primary pulmonary adenocarcinoma.

Aberrant methylation of promoter CpG islands is one of the most important inactivation mechanisms for tumor suppressor and tumor-related genes. Previous studies using genome-wide DNA methylation microarray analysis have suggested the existence of a CpG island methylator phenotype (CIMP) in lung adenocarcinomas. Although the biological behavior of these tumors varies according to tumor stage, no large-scale study has examined the CIMP in lung adenocarcinoma patients according to tumor stage. Furthermore, there have been no reported results regarding the clinical significance of each of the six CIMP markers. To examine the CIMP in patients with pulmonary adenocarcinoma after a surgical resection, we performed methylation analysis of six genes (CCNA1, ACAN, GFRA1, EDARADD, MGC45800, and p16 (INK4A)) in 230 pulmonary adenocarcinoma cases using the SEQUENOM MassARRAY platform. Fifty-four patients (28 %, 54/191) were in the CIMP-high (CIMP-H) group associated with high nodal stage (P = 0.007), the presence of micropapillary or solid histology (P = 0.003), and the absence of an epidermal growth factor receptor (EGFR) mutation (P = 0.002). By multivariate analysis, CIMP was an independent prognostic marker for overall survival (OS) and disease-specific survival (P = 0.03 and P = 0.43, respectively). In the stage I subgroups alone, CIMP-H patients had lower OS rates than the CIMP-low (CIMP-L) group (P = 0.041). Of the six CIMP markers, ACAN alone was significantly associated with patient survival. CIMP predicted the risk of progression independently of clinicopathological variables and enables the stratification of pulmonary adenocarcinoma patients, particularly among stage I cases.

Tumoral pseudogout of the proximal interphalangeal joint of a finger: a case report and literature review.

Tumoral pseudogout is a rare clinical form of calcium pyrophosphate dihydrate crystal deposition disease. Tumoral pseudogout can mimic other diseases such as chondroid tumor, tophaceous gout, or tumoral calcinosis. Its radiological features have been presented in some case reports, but no specific radiographic features have been identified. Here, we report an unusual case of recurrent tumoral pseudogout involving the proximal interphalangeal joint of the right long finger. This case presents with progressive radiological findings of the disease with an enlarging and recurrent calcified mass and secondary bony erosion and remodeling, along with a radiological-pathological correlation. We also review previously reported imaging findings of this disease entity, differential points in comparison to other diseases, and some key points for making the correct diagnosis.

Using immunohistochemistry to assess the accuracy of histomorphologic diagnosis of aspergillosis and mucormycosis.

BACKGROUND: Data on the accuracy of conventional histomorphologic diagnosis are limited, especially in mucormycosis. We therefore investigated the accuracy of histomorphologic diagnosis of mucormycosis and aspergillosis, using immunohistochemistry (IHC) tests for mucormycosis and aspergillosis. METHODS: Patients enrolled met the modified criteria for proven and probable mucormycosis (during a 22-year period) or invasive aspergillosis (during a 6-year period) and had formalin-fixed, paraffin-embedded tissues available. We first tested the diagnostic performance of IHC for mucormycosis and aspergillosis in proven cases. Then we determined the accuracy of histomorphologic diagnosis of probable cases, using the IHC tests. RESULTS: In 7 proven cases of mucormycosis, the sensitivity and specificity of mucormycosis IHC were 100% (95% confidence interval, 65%-100%) and 100% (68%-100%), respectively. In 8 proven cases of aspergillosis, and the sensitivity and specificity of aspergillosis IHC staining were 87% (53%-98%) and 100% (65%-100%), respectively. Of 23 probable mucormycosis cases, 20 (87%) were positive with mucormycosis IHC, 2 (9%) were positive with aspergillosis IHC (including 1 positive for both), and 2 were negative with both. Of 16 probable aspergillosis cases, 10 (63%) were positive with aspergillosis IHC, 4 (25%) were positive with mucormycosis IHC, and 2 (13%) were negative with both tests. CONCLUSIONS: Aspergillosis and mucormycosis seem not to be correctly diagnosed morphologically, because some of the probable cases showed either test with both antibodies or failure to stain with the homologous antibody. In the absence of fungal culture results, the IHC tests seem helpful in differentiating between aspergillosis and mucormycosis.